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Sex Matters

Friday, October 05, 2012

Got your attention didn’t I. A number of years ago, information surfaced suggesting that the majority of human clinical drug studies had been done on males.  This resulted in females receiving drugs based on the results of male studies.  

Could this be considered gender bias, sloppy science, or both? 
It gets even worse: In the case of estrogen replacement therapy (HRT), which depletes B vitamins,  no clinical studies were done before large amounts of estrogen manufactured from pregnant mares’ urine was prescribed by doctors who apparently did not question the lack of clinical science to support what they were recommending to menopausal females daily. One of the reasons might be that the recommendation came with an implied promise of eternal youth, and most women ate that  up.   

Pregnant mare’s urine is metabolized to estradiol in the human female body. 

In the case of women over the age of 60, we were long past burning our bras when we took our first bite from the HRT apple without questioning our doctors or anyone else . . . until a long-overdue Women’s Health Initiative study (WHI) shed frightening new light on hormone replacement therapy. 

This study was stopped midway when it was discovered that the risk for stroke was increased in those women who used HRT. 

After the initial scare, the pharmaceutical companies rallied round, tried hard to change the name from Estrogen Resplacement Therapy (ERT) to Menopause Hormone Therapy (MHR) and convinced doctors that the increased risk of stroke would be lower if they would routinely recommend progestin with estrogen to women who had never had a hysterectomy and found their menopausal symptoms too difficult to deal with naturally.  These women accepted a slight increase in stroke risk and continued to have periods for years after normal cessation of menses. 
Slight risk proved to be wrong, based on a 2010 JAMA study that found the risk for stroke still existed, and they also found the risk for developing breast cancer twice as high in postmenopausal women who were taking estrogen plus some progestin.

Understand Biology Also Matters 

Estradiol (E2) is the predominant estrogen during reproductive years in estrogenic activity. Estradiol is also present in males as a metabolic by-product of testosterone, with the normal serum levels of males being about the same in untreated postmenopausal women.  It has been known for years that the reproductive hormone estradiol is synthesized in the hippocampus of both males and females, where it affects hippocampal functions such as memory and mood-related behavior by increasing the excitability of neurons. 

Roll the Clock Forward:  

A study just published in the June 2012 issue of Neuron revealed a synaptic modulation pathway in the hippocampus that seems to be exclusive to females. 

Two brilliant scientists at Northwestern University, Guang Zhe Haung and Catherine Woolley, recorded electrical signals from rat hippocampal slices exposed to estradiol and found that in addition to its excitatory effects, estradiol suppressed inhibitory synaptic transmission, which could explain HRT sensations reported by some females as stepping on the gas and disabling the brakes at the same time (the study authors’ description, not mine).
Based on previous science, these two researchers believed that estradiol acts on inhibitory neurons by enlisting compounds called endocannabinoids.  Imagine their shock when their results were different than the ones observed in previous studies of estradiol /hippocampal signaling. The reason for the disparity: all the earlier studies were done on male rats, and these researchers were using female rats. 

Does this explain the stepping on the gas and disabling the brakes sensations described by some women  on hormone therapies?  And does it shed light on some women's inability to control the overwhelming desire to consume excessive amounts of food a few days every month?  Could this explain weight gain in women who continue  hormone therapy long after menopause? 

A professor at the University of Minnesota, Paul Mermelstein, pointed out that the vast majority of basic neuroscience experiments have been done on male animals, “There may be a whole infrastructure in terms of endocannabinoid signaling present in the female brain that’s not present in males.” 
For those of you who may wonder what this column has to do with  nutrition, read the PEARL below.

Ellen Troyer, MT MA
Biosyntrx CEO / Chief Research Officer


Interestingly, a literature search of post-publication research on the data collected by the Vitamins and Lifestyle (VITAL) study teased out a number of studies that sadly link HRT to an increased risk of a number of different types of cancer and stroke.  I felt it was worth addressing and included a few of these studies  in the references bacause menopausal and post menopausal women represent more than 65% of our customer base. 

It could be a Mars & Venus thing where naturally occuring endocannabinoids are concerned.  Both humans and animals naturally synthesize endocannabinoids, the chemical compounds that activate the same receptors as delta-9-tetrahydrocannabinol (THC)  – yes, we are talking about Cannabis sativa).  There is a growing body of evidence to support the role naturally occurring endocannabinoids, and plant-based THC play in iinsomnia, pain and anxiety control. Community based medical cannabis dispensaries have proven successful at supplying patients with a safe source of cannabis within an environment conductive to healing, and may be reducing the huge numbers of people who suffer pharmaceutical opiate addictions. 

Data You May Find Interesting From the March 02, 2012  Friday Pearl

The January 2012 Centers for Disease Control and Prevention (CDC) Morbidity and Mortality Weekly Report suggests in their CDC Grand Rounds called: Prescription Drug Overdoses – A U.S. Epidemic, that approximately 27,000 unintentional drug overdose deaths occurred in the United States in 2007, one death every 19 minutes (one wonders why they don’t have data newer than 2007 since they are calling this an epidemic). 

The 2007 report identified that more overdose deaths involved prescription drug opiod analgesics than heroin and cocaine combined.  They also reported that for every unintentional overdose death related to an opiod analgesic, nine persons were admitted for substance abuse treatment (243,000), 35 visited emergency departments (945,000) and 161 reported drug abuse or dependence (4,347,000), and 461 reported non-medical use of opiod analgesics (12,447,000). 


Estradiol Acutely Suppresses Inhibition in the Hippocampus through a Sex-Specific Endocannabinoid and mGluR-Dependent Mechanism. Haung GZ, Woodley C, Neuron June 2012; 74;(5) 801-808 [abstract]

Vitamin, mineral, and specialty supplements and risk of hematologic malignancies in the prospective Vitamins and Lifestyle (VITAL) study, Walter, R, Brasky T, et al.  Cancer Epidemol Biomarkers. Prev. [full study]

Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. Nelson HD, Walter M, et al. Ann Intern Med. 2012 Jul 17; 157(2): 104013 [full study]

Lung Cancer and Hormone Replacement Therapy: Association in the Vitamins and Lifestyle Study. Slatore C, Chien J, et al. J Clin Oncol. 2010 March 20; 28(9): 1540-1546. [full study]

Estrogen Plus Progestin Therapy and Breast Cancer in Recently Postmenopausal Women. Prentice R, Chlebowski R, et al. Am J Epidemio. 2008, May 15; 167(10): 1297-1216  [full study] 

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Key TH, Appleby, PN et al.  Br J Cancer 2011 August 23; 105(5): 709-772 [full study]

Endocannabinoid Studies

Endocannabinoids in the Retina: From Marijuana to Neuroprotection. Yazulla, S. Prog Retin Eye Res. 2008 September: 27(S): 501-526.
 [full study]

Estrogenic Plant Extracts Reverse Weight Gain and Fat Accumulation Without Causing Mammary Gland or Uterine Proliferation. Saunier E. Vivar O, et al. Plow One. 2011; 8(12): [full study]